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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Smc hinge domain	0	DIRECT
Orange domain-like	0	DIRECT
ARID-like	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Second domain of FERM	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
TIMP-like	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
MIR domain	0	DIRECT
Cullin repeat-like	0	DIRECT
L27 domain	0	DIRECT
Serpins	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Mob1/phocein	0	DIRECT
Sema domain	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
SMAD MH1 domain	0	DIRECT
Integrin domains	0	DIRECT
Plexin repeat	0	DIRECT
SAP domain	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Cullin homology domain	0	DIRECT
PreATP-grasp domain	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
SAICAR synthase-like	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Rhomboid-like	0	DIRECT
Cytokine	0	DIRECT
Homeodomain-like	0.00000000002783	DIRECT
beta-beta-alpha zinc fingers	0.000001014	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000002602	DIRECT
Fibronectin type III	0.0002465	DIRECT
Protein kinase-like (PK-like)	0.0009518	DIRECT
Immunoglobulin	0.00107	INHERITED FROM: synaptic neuropil || lobe system of adult mushroom body || antennal lobe glomerulus || nerve || commissure || LNv neuron || connective || neuropil glial sheath || abdominal segmental nerve || LN period neuron || central nervous system || abdominal nerve || leg taste bristle chemosensory neuron || tract neuropil || adult brain
Glucocorticoid receptor-like (DNA-binding domain)	0.005736	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.005881	INHERITED FROM: midline crossing tract || ommatidium || adult peripheral nervous system || photoreceptor cell R7
p53-like transcription factors	0.008166	INHERITED FROM: mesothoracic tergum || adult external thorax || tagmatic subdivision of integument
Nuclear receptor ligand-binding domain	0.008166	INHERITED FROM: synaptic neuropil || synaptic neuropil block || central brain || mushroom body gamma-lobe || supraesophageal ganglion neuron || protocerebrum || neuropil
PH domain-like	0.01653	INHERITED FROM: embryonic foregut
HMG-box	0.03399	INHERITED FROM: adult external thorax || wing
Cystine-knot cytokines	0.05857	INHERITED FROM: embryonic/larval posterior spiracle || embryonic/larval spiracle || stigmatophore
EGF/Laminin	0.07986	INHERITED FROM: wing blade || embryonic/larval midgut cell || ocellus || tendon cell || proventriculus || adult midgut progenitor cell || ventral nervous system || larval caeca region || eye photoreceptor cell stalk
Transducin (alpha subunit), insertion domain	0.182	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.182	INHERITED FROM: ventral nerve cord
Snake toxin-like	0.182	INHERITED FROM: embryonic/larval neuromuscular junction || wing cell || tarsal segment || wing vein || neuromuscular junction || embryonic/larval peripheral nervous system
Growth factor receptor domain	0.2265	INHERITED FROM: embryonic fiber tract || ocellus || hindgut || embryonic/larval midline of ventral nerve cord || dMP2 neuron || proventriculus || RP2sib neuron || integumentary specialisation || ventral midline || ocellar triangle || ventral nervous system || wing vein L2 || photoreceptor cell R7 || vMP2 neuron || surface associated glial cell
Spectrin repeat	0.2517	INHERITED FROM: tract || middle midgut || connective || midgut epithelium || longitudinal connective || ipsilateral tract || copper cell
vWA-like	0.3134	INHERITED FROM: endocuticular specialization
Cytochrome P450	0.3516	INHERITED FROM: midline glial cell || hindgut || midline crossing tract || commissure || tract || neuropil glial sheath || neuropil associated CNS glial cell || CNS glial cell || midgut || larval neuropil glial cell || tract neuropil || embryonic/larval foregut || larval VNC neuropil glial cell || embryonic/larval hindgut
HAD-like	0.3765	INHERITED FROM: rhabdomere of eye photoreceptor cell
(Phosphotyrosine protein) phosphatases II	0.4142	INHERITED FROM: medial lobe of adult mushroom body || intersegmental nerve
SET domain	0.4209	INHERITED FROM: metathoracic leg || haltere
dsRNA-binding domain-like	0.4405	INHERITED FROM: adult uniglomerular antennal lobe projection neuron adPN || persistent antennal lobe projection neuron || projection neuron || alpha/beta Kenyon cell || unilateral ACT relay interneuron || mushroom body extrinsic neuron || adult MBp lineage neuron || antennal lobe projection neuron || adult MBp lineage clone || uniglomerular antennal lobe projection neuron || medial antennal lobe tract projection neuron || adult antennal lobe projection neuron DL1 adPN || adult antennal lobe projection neuron || adult antennal lobe projection neuron adPN || Kenyon cell || antennal lobe projection neuron adPN
BAR/IMD domain-like	0.4405	INHERITED FROM: NMJ bouton || neuromuscular junction
Cadherin-like	0.5019	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9695	INHERITED FROM: adult antennal nerve || antennal nerve

Family domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Myb/SANT domain	0	DIRECT
RNase III catalytic domain-like	0	DIRECT
BC ATP-binding domain-like	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase, UCH	0	DIRECT
Phosphatidylinositol phosphate kinase IIbeta, PIPK IIbeta	0	DIRECT
Third domain of FERM	0	DIRECT
p120GAP domain-like	0	DIRECT
Single strand DNA-binding domain, SSB	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Rel/Dorsal transcription factors, DNA-binding domain	0	DIRECT
First domain of FERM	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
SCF ubiquitin ligase complex WHB domain	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
Dachshund-homology domain	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
Phoshoinositide 3-kinase (PI3K), catalytic domain	0	DIRECT
PX domain	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
SMAD MH1 domain	0	DIRECT
Cullin homology domain	0	DIRECT
Serpins	0	DIRECT
Synaptotagmin-like (S variant)	0	DIRECT
Class I glutamine amidotransferases (GAT)	0	DIRECT
SPRY domain	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Forkhead DNA-binding domain	0	DIRECT
ARID domain	0	DIRECT
Diacylglycerol kinase-like	0	DIRECT
NF-kappa-B/REL/DORSAL transcription factors, C-terminal domain	0	DIRECT
Plexin repeat	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
BC N-terminal domain-like	0	DIRECT
Transforming growth factor (TGF)-beta	0	DIRECT
Sema domain	0	DIRECT
Hairy Orange domain	0	DIRECT
L27 domain	0	DIRECT
EF-hand modules in multidomain proteins	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Laminin-type module	0	DIRECT
POU-specific domain	0	DIRECT
Mob1/phocein	0	DIRECT
Rhomboid-like	0	DIRECT
Smc hinge domain	0	DIRECT
SAP domain	0	DIRECT
L-arabinose binding protein-like	0	DIRECT
Integrin domains	0	DIRECT
Pepsin-like	0	DIRECT
Cell cycle control phosphatase, catalytic domain	0	DIRECT
Phosphate binding protein-like	0	DIRECT
Cullin repeat	0	DIRECT
cAMP-binding domain	0	DIRECT
Second domain of FERM	0	DIRECT
Arrestin/Vps26-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase UCH-L	0	DIRECT
Phoshoinositide 3-kinase (PI3K) helical domain	0	DIRECT
MIR domain	0	DIRECT
Homeodomain	0.0000000000006665	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000004491	DIRECT
Fibronectin type III	0.000355	DIRECT
Protein kinases, catalytic subunit	0.0009293	DIRECT
Classic zinc finger, C2H2	0.00301	INHERITED FROM: region of integument
SH2 domain	0.00652	INHERITED FROM: midline crossing tract || ommatidium || adult peripheral nervous system || photoreceptor cell R7
Nuclear receptor ligand-binding domain	0.008292	INHERITED FROM: synaptic neuropil || synaptic neuropil block || central brain || mushroom body gamma-lobe || supraesophageal ganglion neuron || protocerebrum || neuropil
Nuclear receptor	0.02051	INHERITED FROM: synaptic neuropil || synaptic neuropil block || mushroom body gamma-lobe || supraesophageal ganglion neuron || abdominal neuromere || larval abdominal neuromere
HMG-box	0.03456	INHERITED FROM: region of integument || adult external thorax || wing
Ngr ectodomain-like	0.05331	INHERITED FROM: intersegmental nerve branch ISNb of A1-7 || abdominal intersegmental nerve || intersegmental nerve of A1-7
Paired domain	0.05331	INHERITED FROM: EG neuron || RP2 motor neuron || EL neuron
Higher-molecular-weight phosphotyrosine protein phosphatases	0.05331	INHERITED FROM: intersegmental nerve
I set domains	0.06878	INHERITED FROM: interface glial cell || segmental subdivision of organ system || synaptic neuropil || lobe system of adult mushroom body || antennal lobe glomerulus || synaptic neuropil subdomain || commissure || adult cerebral ganglion || synaptic neuropil block || LNv neuron || connective || neuropil glial sheath || adult central nervous system || s-LNv neuron || gustatory receptor neuron || leg taste bristle chemosensory neuron || tract neuropil || adult brain
PLC-like (P variant)	0.09608	INHERITED FROM: mesothoracic tergum || larval dorsal multidendritic neuron ddaC || larval dorsal multidendritic neuron
Histone lysine methyltransferases	0.09608	INHERITED FROM: metathoracic leg || haltere
BTB/POZ domain	0.1339	INHERITED FROM: prothoracic tarsal segment
Laminin G-like module	0.1552	INHERITED FROM: photoreceptor cell R4
Transducin (alpha subunit), insertion domain	0.1721	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1721	INHERITED FROM: ventral nerve cord
SMAD domain	0.231	INHERITED FROM: wing blade || wing vein || gut section
Ankyrin repeat	0.2359	INHERITED FROM: ventral multidendritic neuron
Spectrin repeat	0.2467	INHERITED FROM: tract || middle midgut || connective || midgut epithelium || longitudinal connective || ipsilateral tract || copper cell
SAM (sterile alpha motif) domain	0.3085	INHERITED FROM: prothoracic leg || mesothoracic leg || metatarsus || sex comb || metatarsus of male prothoracic leg || prothoracic metatarsus || prothoracic tarsal segment
Calponin-homology domain, CH-domain	0.3274	INHERITED FROM: abdominal segmental nerve
Cytochrome P450	0.3531	INHERITED FROM: midline glial cell || hindgut || midline crossing tract || commissure || tract || neuropil glial sheath || neuropil associated CNS glial cell || CNS glial cell || midgut || larval neuropil glial cell || tract neuropil || embryonic/larval foregut || larval VNC neuropil glial cell || embryonic/larval hindgut
Cyclin	0.3896	INHERITED FROM: tagmatic subdivision of organ system
Growth factor receptor domain	0.4227	INHERITED FROM: salivary gland || ocellus || hindgut || proventriculus || integumentary specialisation || ocellar triangle || tibia
EGF-type module	0.5404	INHERITED FROM: wing blade || embryonic/larval midgut cell || hindgut || proventriculus || adult midgut progenitor cell || adult external head || ventral nervous system
Ubiquitin-related	0.5594	INHERITED FROM: mushroom body extrinsic neuron
Cadherin	0.5903	INHERITED FROM: wing hair || outer photoreceptor cell || photoreceptor cell R4
G proteins	0.9379	INHERITED FROM: wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
Multidrug resistance efflux transporter EmrE	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Smc hinge domain	0	DIRECT
SMAD MH1 domain	0	DIRECT
Cytokine	0	DIRECT
ARID-like	0	DIRECT
MIR domain	0	DIRECT
Plexin repeat	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Orange domain-like	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
SAP domain	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Serpins	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
TIMP-like	0	DIRECT
Cullin homology domain	0	DIRECT
Rhomboid-like	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Cullin repeat-like	0	DIRECT
L27 domain	0	DIRECT
Sema domain	0	DIRECT
SAICAR synthase-like	0	DIRECT
PreATP-grasp domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
Mob1/phocein	0	DIRECT
Second domain of FERM	0	DIRECT
Integrin domains	0	DIRECT
Homeodomain-like	0.00000000001998	DIRECT
beta-beta-alpha zinc fingers	0.0000007354	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00000189	DIRECT
Fibronectin type III	0.0001804	DIRECT
Protein kinase-like (PK-like)	0.000689	DIRECT
Immunoglobulin	0.0007709	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.004169	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.004284	INHERITED FROM: adult peripheral nervous system || connective || midline crossing tract || tract || photoreceptor cell R7 || ommatidium
Nuclear receptor ligand-binding domain	0.005995	INHERITED FROM: synaptic neuropil block || synaptic neuropil || supraesophageal ganglion neuron || protocerebrum || neuropil || mushroom body gamma-lobe || central brain
p53-like transcription factors	0.005995	INHERITED FROM: integumentary process || tagmatic subdivision of integument || tract || adult external thorax || mesothoracic tergum
PH domain-like	0.01256	INHERITED FROM: embryonic foregut
HMG-box	0.02665	INHERITED FROM: wing || adult external thorax
Cystine-knot cytokines	0.04726	INHERITED FROM: embryonic/larval spiracle || embryonic/larval posterior spiracle || spiracle || stigmatophore
EGF/Laminin	0.06563	INHERITED FROM: proventriculus || wing blade || adult midgut progenitor cell || eye photoreceptor cell stalk || ventral nervous system || tendon cell || larval caeca region || ocellus || embryonic/larval midgut cell
GTPase activation domain, GAP	0.1096	INHERITED FROM: abdominal intersegmental nerve
Transducin (alpha subunit), insertion domain	0.1579	INHERITED FROM: eo neuron
Snake toxin-like	0.1579	INHERITED FROM: embryonic/larval peripheral nervous system || wing cell || embryonic/larval neuromuscular junction || neuromuscular junction || adult optic lobe || wing vein || tarsal segment
Toll/Interleukin receptor TIR domain	0.1579	INHERITED FROM: ventral nerve cord
Growth factor receptor domain	0.1988	INHERITED FROM: fascicle || embryonic/larval midline of ventral nerve cord || embryonic fiber tract || proventriculus || ventral midline || retinal pigment cell || RP2sib neuron || hindgut || surface associated glial cell || ventral nervous system || wing vein L2 || ocellar triangle || wing vein L4 || ocellus || photoreceptor cell R7 || dMP2 neuron || vMP2 neuron || integumentary specialisation
Spectrin repeat	0.2228	INHERITED FROM: copper cell || connective || midgut epithelium || longitudinal connective || tract || ipsilateral tract || middle midgut
vWA-like	0.2822	INHERITED FROM: endocuticular specialization
Calponin-homology domain, CH-domain	0.2878	INHERITED FROM: abdominal segmental nerve
Cytochrome P450	0.3199	INHERITED FROM: embryonic/larval foregut || larval VNC neuropil glial cell || midline crossing tract || tract neuropil || midgut || neuropil associated CNS glial cell || larval neuropil glial cell || hindgut || tract || embryonic/larval hindgut || CNS glial cell || neuropil glial sheath || commissure || midline glial cell
HAD-like	0.3442	INHERITED FROM: rhabdomere of eye photoreceptor cell
(Phosphotyrosine protein) phosphatases II	0.3816	INHERITED FROM: intersegmental nerve || medial lobe of adult mushroom body
SET domain	0.3884	INHERITED FROM: haltere || metathoracic leg
dsRNA-binding domain-like	0.4081	INHERITED FROM: adult MBp lineage neuron || antennal lobe projection neuron || adult antennal lobe projection neuron DL1 adPN || Kenyon cell || adult uniglomerular antennal lobe projection neuron adPN || mushroom body extrinsic neuron || unilateral ACT relay interneuron || adult antennal lobe projection neuron adPN || adult MBp lineage clone || adult antennal lobe projection neuron || medial antennal lobe tract projection neuron || uniglomerular antennal lobe projection neuron || alpha/beta Kenyon cell || projection neuron || antennal lobe projection neuron adPN || persistent antennal lobe projection neuron
BAR/IMD domain-like	0.4081	INHERITED FROM: NMJ bouton || neuromuscular junction
Cadherin-like	0.4699	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9635	INHERITED FROM: adult antennal nerve || antennal nerve

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0	DIRECT
47769,47769 47769 - SAM/Pointed domain 47769 - SAM/Pointed domain	0	DIRECT
57903,47370 57903 - FYVE/PHD zinc finger 47370 - Bromodomain	0	DIRECT
52058,48726 52058 - L domain-like 48726 - Immunoglobulin	0	DIRECT
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
49417,81296 49417 - p53-like transcription factors 81296 - E set domains	0	DIRECT
48403,48403 48403 - Ankyrin repeat 48403 - Ankyrin repeat	0	DIRECT
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
54236,47031 54236 - Ubiquitin-like 47031 - Second domain of FERM	0	DIRECT
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0	DIRECT
47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
48371,56112 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
49265,49265 49265 - Fibronectin type III 49265 - Fibronectin type III	0	DIRECT
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0	DIRECT
55550,50044 55550 - SH2 domain 50044 - SH3-domain	0	DIRECT
75632,46785 75632 - Cullin homology domain 46785 - "Winged helix" DNA-binding domain	0	DIRECT
74788,75632 74788 - Cullin repeat-like 75632 - Cullin homology domain	0	DIRECT
52058,52058 52058 - L domain-like 52058 - L domain-like	0	DIRECT
81660,56784 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like	0	DIRECT
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0	DIRECT
49562,48371 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat	0	DIRECT
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0	DIRECT
51045,51045 51045 - WW domain 51045 - WW domain	0	DIRECT
47031,50729 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
48425,50729 48425 - Sec7 domain 50729 - PH domain-like	0	DIRECT
52440,56059 52440 - PreATP-grasp domain 56059 - Glutathione synthetase ATP-binding domain-like	0	DIRECT
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0	DIRECT
51206,51206 51206 - cAMP-binding domain-like 51206 - cAMP-binding domain-like	0	DIRECT
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.000003009	DIRECT
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.01269	INHERITED FROM: s-LNv neuron || synaptic neuropil block || segmental subdivision of organ system || synaptic neuropil || LN period neuron || leg taste bristle chemosensory neuron || connective || lobe system of adult mushroom body || tract neuropil || antennal lobe glomerulus || LNv neuron || central nervous system || adult cerebral ganglion || neuropil glial sheath || commissure || adult brain
48726,49265 48726 - Immunoglobulin 49265 - Fibronectin type III	0.04231	INHERITED FROM: s-LNv neuron || adult antennal lobe || LN period neuron || leg taste bristle chemosensory neuron || adult antennal lobe glomerulus || connective || lobe system of adult mushroom body || tract neuropil || antennal lobe glomerulus || neuropil associated CNS glial cell || LNv neuron || giant fiber neuron || neuropil glial sheath || commissure || gustatory receptor neuron
49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0.06191	INHERITED FROM: photoreceptor cell R4 || peripheral nervous system
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.08471	INHERITED FROM: copper cell || connective || tract neuropil || midgut epithelium || longitudinal connective || tract || adult protocerebrum || ipsilateral tract || middle midgut
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.1579	INHERITED FROM: intersegmental nerve || proventriculus || scutum || wing blade dorsal compartment || inner photoreceptor cell || wing vein || leg || joint || photoreceptor cell R7 || integumentary specialisation
47459,55785 47459 - HLH, helix-loop-helix DNA-binding domain 55785 - PYP-like sensor domain (PAS domain)	0.1579	INHERITED FROM: sclerite
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1579	INHERITED FROM: eo neuron
54928,54928 54928 - RNA-binding domain, RBD 54928 - RNA-binding domain, RBD	0.1988	INHERITED FROM: bristle of mesothoracic tergum
81296,81296 81296 - E set domains 81296 - E set domains	0.2154	INHERITED FROM: abdominal segmental nerve || intersegmental nerve || abdominal nerve || segmental nerve || abdominal intersegmental nerve
52799,52799 52799 - (Phosphotyrosine protein) phosphatases II 52799 - (Phosphotyrosine protein) phosphatases II	0.2924	INHERITED FROM: abdominal segmental nerve || intersegmental nerve || abdominal nerve || segmental nerve || embryonic/larval peripheral nervous system || nerve
50156,50044 50156 - PDZ domain-like 50044 - SH3-domain	0.2924	INHERITED FROM: embryonic/larval peripheral nervous system
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.3073	INHERITED FROM: tertiary pigment cell || proventriculus || wing blade dorsal compartment || secondary pigment cell || intersegmental nerve branch ISNb of A1-7 || eye photoreceptor cell stalk || ventral nervous system || postfrons || joint || frons || ocellus
57184,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.3577	INHERITED FROM: integumentary specialisation
49313,49313 49313 - Cadherin-like 49313 - Cadherin-like	0.5592	INHERITED FROM: wing hair || outer photoreceptor cell || photoreceptor cell R4

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
49562,48371,56112 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
57196,49899,49899 57196 - EGF/Laminin 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
74788,75632,46785 74788 - Cullin repeat-like 75632 - Cullin homology domain 46785 - "Winged helix" DNA-binding domain	0	DIRECT
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0	DIRECT
81660,56784,81665 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like 81665 - Calcium ATPase, transmembrane domain M	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0	DIRECT
54236,47031,50729 54236 - Ubiquitin-like 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
49899,49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00007977	DIRECT
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.06563	INHERITED FROM: s-LNv neuron || synaptic neuropil block || segmental subdivision of organ system || synaptic neuropil || leg taste bristle chemosensory neuron || connective || lobe system of adult mushroom body || tract neuropil || LNv neuron || central nervous system || commissure || adult brain || gustatory receptor neuron
48726,48726,49265 48726 - Immunoglobulin 48726 - Immunoglobulin 49265 - Fibronectin type III	0.08725	INHERITED FROM: s-LNv neuron || adult antennal lobe || LN period neuron || leg taste bristle chemosensory neuron || adult antennal lobe glomerulus || connective || lobe system of adult mushroom body || antennal lobe glomerulus || neuropil associated CNS glial cell || LNv neuron || giant fiber neuron || eo neuron || embryonic/larval central nervous system || neuropil glial sheath || gustatory receptor neuron
57196,57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin 57196 - EGF/Laminin	0.1044	INHERITED FROM: photoreceptor cell R6 || photoreceptor cell R1 || tertiary pigment cell || proventriculus || wing blade dorsal compartment || secondary pigment cell || adult external head || eye photoreceptor cell stalk || ventral nervous system || ocellar triangle || postfrons || joint || frons || ocellus
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.2154	INHERITED FROM: intersegmental nerve || bristle of mesothoracic tergum || dorsal mesothorax || scutum || tergum || adult external mesothorax || adult thoracic mechanosensory chaeta || mesothoracic tergum || nerve || integumentary specialisation
49313,49313,49313 49313 - Cadherin-like 49313 - Cadherin-like 49313 - Cadherin-like	0.5592	INHERITED FROM: wing hair || outer photoreceptor cell || photoreceptor cell R4

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.